Metabolism studies are proposed for four classes of anticonvulsants that are used to reduce the intensity and susceptibility of epileptic seizures. The barbiturates, hydantoins, succinimides and oxazolidienediones will be investigated with molecular orbital methods to determine metabolic products of nucleophilic and electrophilic hydrolysis. The prediction of metabolites will be based on the energies and bonding patterns for the highest occupied and lowest empty molecular orbitals. The predicted metabolites will be investigated to determine the physical characteristics of each metabolite. The preferred conformation, net atom charges and dipole moments will come directly from the molecular orbital calculations. The proposed research will assist in determining whether a link exists between the predicted metabolites of the above classes of anticonvulsants and the inhibitory transmitter, gamma aminobutyric acid, GABA. GABA has recently been related to seizure susceptibility. One aim of the project is the improved design of anticonvulsant compounds. An improved understanding of structure activity relationships for anticonvulsants is essential. The research will provide information concerning the ability of selected aryl and alkye substituents of these anticonvulsant agents to effect metabolism. The knowledge of the role of the large bulky substituents required for efficacy in influencing and directing metabolism will assist in the design of drug compounds capable of increased or decreased levels of metabolism.